Jonathan Naftali, Amir Glik, Ruth Eliahou, Gil D Rabninovici, Howar J Rosen, Fanny Elahi, Felix Benninger, Ilan Goldberg, Eitan Auriel, Ophir Keret
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Each CSVD marker was modeled for interaction with group age on results on cognitive outcomes: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory Questionnaire (NPI-Q), and Clinical Dementia Rating (CDR) scale plus National Alzheimer's Coordinating Center–Frontotemporal Lobar Degeneration module (NACC-FTLD).</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Altogether, 168 patients (91 EO) were included. white matter hyperintensity (WMH) volume was associated with worse CDR+NACC-FTLD in EO (<i>β </i>= 17.8, <i>p </i>= 0.013), remaining significant after adjusting for p-tau217 and NfL, but not gray matter atrophy. Lacunes were associated with worse CDR plus NACC-FTLD in EO (<i>β </i>= 4.3, <i>p </i>= 0.011), with age-dependent associations with MoCA, MMSE, CDR + NACC-FTLD, and NPI-Q (<i>p</i> < 0.01).</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>CSVD markers, although less prevalent in EO, had greater clinical impact. These findings highlight an increased vulnerability to vascular pathology in EO patients and the importance of early detection.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Cerebral small vessel disease (CSVD) markers were more impactful in early-onset than late-onset dementia.</li>\n \n <li>White matter hyperintensity (WMH) volume predicted functional decline in early onset, independent of neurodegeneration.</li>\n \n <li>Lacunes showed age-dependent effects on multiple cognitive outcomes.</li>\n \n <li>Findings support early detection of CSVD in younger individuals with dementia.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 10","pages":""},"PeriodicalIF":11.1000,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519510/pdf/","citationCount":"0","resultStr":"{\"title\":\"Impact of cerebral small vessel disease on cognitive outcomes in early age at onset MCI and dementia: Findings from the DIASPORA study\",\"authors\":\"Jonathan Naftali, Amir Glik, Ruth Eliahou, Gil D Rabninovici, Howar J Rosen, Fanny Elahi, Felix Benninger, Ilan Goldberg, Eitan Auriel, Ophir Keret\",\"doi\":\"10.1002/alz.70773\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> BACKGROUND</h3>\\n \\n <p>This study assessed the impact of cerebral small vessel disease (CSVD) on cognition in individuals with early-onset (EO; <65 years) and late-onset (LO; ≥65 years) cognitive complaints.</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>Participants underwent prospective evaluations including cognitive testing, hyperphosphorylated tau-217 (p-tau217) and neurofilament-light-chain (NfL), and magnetic resonance imaging (MRI). 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引用次数: 0
摘要
背景：本研究评估了早发性脑血管病（CSVD）对认知的影响；方法：参与者进行了前瞻性评估，包括认知测试、高磷酸化tau-217 （p-tau217）和神经丝轻链（NfL）以及磁共振成像（MRI）。每个CSVD标志物与组年龄的相互作用根据认知结果建模：蒙特利尔认知评估（MoCA）、迷你精神状态检查（MMSE）、神经精神量表（NPI-Q）和临床痴呆评分（CDR）量表加上国家阿尔茨海默病协调中心-额颞叶变性模块（NACC-FTLD）。结果：共纳入168例患者（91例EO）。白质高强度（WMH）体积与EO患者更差的CDR+NACC-FTLD相关（β = 17.8, p = 0.013），在调整p-tau217和NfL后仍然显著，但与灰质萎缩无关。在EO中，腔隙与较差的CDR + NACC-FTLD相关（β = 4.3, p = 0.011），与MoCA、MMSE、CDR + NACC-FTLD和NPI-Q存在年龄依赖性关联(p讨论：CSVD标志物虽然在EO中不太普遍，但具有更大的临床影响。这些发现强调了EO患者对血管病理的易感性增加以及早期发现的重要性。重点：脑血管病（CSVD）标志物对早发性痴呆的影响大于晚发性痴呆。白质高强度（WMH）体积预测早期发病的功能下降，独立于神经退行性变。Lacunes对多种认知结果显示出年龄依赖性。研究结果支持在年轻痴呆患者中早期发现CSVD。
Impact of cerebral small vessel disease on cognitive outcomes in early age at onset MCI and dementia: Findings from the DIASPORA study
BACKGROUND
This study assessed the impact of cerebral small vessel disease (CSVD) on cognition in individuals with early-onset (EO; <65 years) and late-onset (LO; ≥65 years) cognitive complaints.
METHODS
Participants underwent prospective evaluations including cognitive testing, hyperphosphorylated tau-217 (p-tau217) and neurofilament-light-chain (NfL), and magnetic resonance imaging (MRI). Each CSVD marker was modeled for interaction with group age on results on cognitive outcomes: Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory Questionnaire (NPI-Q), and Clinical Dementia Rating (CDR) scale plus National Alzheimer's Coordinating Center–Frontotemporal Lobar Degeneration module (NACC-FTLD).
RESULTS
Altogether, 168 patients (91 EO) were included. white matter hyperintensity (WMH) volume was associated with worse CDR+NACC-FTLD in EO (β = 17.8, p = 0.013), remaining significant after adjusting for p-tau217 and NfL, but not gray matter atrophy. Lacunes were associated with worse CDR plus NACC-FTLD in EO (β = 4.3, p = 0.011), with age-dependent associations with MoCA, MMSE, CDR + NACC-FTLD, and NPI-Q (p < 0.01).
DISCUSSION
CSVD markers, although less prevalent in EO, had greater clinical impact. These findings highlight an increased vulnerability to vascular pathology in EO patients and the importance of early detection.
Highlights
Cerebral small vessel disease (CSVD) markers were more impactful in early-onset than late-onset dementia.
White matter hyperintensity (WMH) volume predicted functional decline in early onset, independent of neurodegeneration.
Lacunes showed age-dependent effects on multiple cognitive outcomes.
Findings support early detection of CSVD in younger individuals with dementia.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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